Although a small number of variants in ethanol metabolism genes have a large impact on risk for AUD, 40 the vast majority of variants are more common but do not exhibit substantial risk on their own; however, collectively multiple SNPs (i.e., polygenic) likely contribute to the genetic risk of AUD. The identification of these multiple variants will help predict the onset and development of individual risk for dependence. 71 , 72 A polygenic risk score (PGS) estimates the risk of an individual to develop a disorder based on contributions of multiple risk‐associated variants throughout the genome 73 (also see 4. Genetics in this issue). A recent study by Page et al. 74 used a human iPSC approach to evaluate the combined functional effects of multiple schizophrenia‐associated variants by comparing iPSC‐derived cortical neurons from individuals affected by schizophrenia who had a high PGS for SCZ and neurotypical individuals with low PGS for SCZ. They observed differences in the function of sodium channels, excitability, and GABAergic neurotransmission, 74 suggesting that PGS captures some of the molecular mechanisms underlying schizophrenia.
